Cardiac papillary fibroelastoma: a comprehensive analysis of 725 cases

Cardiac papillary fibroelastoma: A comprehensive analysis of 725 cases Ramesh M. Gowda, MD,a Ijaz A. Khan, MD, FACP, FACC,b Chandra K. Nair, MD, FACP, FACC,b Nirav J. Mehta, MD,b Balendu C. Vasavada, MD, FACC,a and Terrence J. Sacchi, MD, FACCa Omaha, Neb, and Brooklyn, NY

Background

With the advent of echocardiography, cardiac papillary fibroelastoma (CPF) is being increasingly reported. The demographics, clinical characteristics, pathological features, treatment, and prognosis of CPF are examined.

Data collection

Cases, case series and related articles on the subject in all languages were identified through a comprehensive literature search.

Results and Conclusions

Seven hundred twenty-five cases of CPF were identified. Males comprised 55% of patients. Highest prevalence was in the 8th decade of life. The valvular surface was the predominant locations of tumor. The most commonly involved valve was the aortic valve, followed by the mitral valve. The left ventricle was the predominant nonvalvular site involved. No clear risk factor for development of CPF has been reported. Size of the tumor varied from 2 mm to 70 mm. Clinically, CPFs have presented with transient ischemic attack, stroke, myocardial infarction, sudden death, heart failure, presyncope, syncope, pulmonary embolism, blindness, and peripheral embolism. Tumor mobility was the only independent predictor of CPF-related death or nonfatal embolization. Symptomatic patients should be treated surgically because the successful complete resection of CPF is curative and the long-term postoperative prognosis is excellent. The symptomatic patients who are not surgical candidates could be offered long-term oral anticoagulation, although no randomized controlled data are available on its efficacy. Asymptomatic patients could be treated surgically if the tumor is mobile, as the tumor mobility is the independent predictor of death or nonfatal embolization. Asymptomatic patients with nonmobile CPF could be followed-up closely with periodic clinical evaluation and echocardiography, and receive surgical intervention when symptoms develop or the tumor becomes mobile. (Am Heart J 2003;146:404 –10.)

Primary tumors of the heart are rare. Based upon the data of 22 large autopsy series, the frequency of primary cardiac tumors is approximately 0.02%, corresponding to 200 tumors in 1 million autopsies.1,2 Cardiac papillary fibroelastomas (CPF), the second most common primary cardiac tumors, are benign endocardial papillomas predominantly affecting the cardiac valves, and account for three fourths of all cardiac valvular tumors. They consist of a small, highly papillary, pedunculated and avascular tumor, covered by a single layer of endothelium, containing variable amounts of fine elastic fibrils arranged in whorls in a hyaline stroma. The majority of patients with CPF are asymptomatic. The advent of echocardiography has allowed From the aDivision of Cardiology, Long Island College Hospital, Brooklyn, NY and the b Division of Cardiology, Creighton University School of Medicine, Omaha, Neb. Submitted September 24, 2002; accepted December 12, 2002. Reprint requests: Ijaz A. Khan, MD, FACP, FACC, Creighton University Cardiac Center, 3006 Webster Street, Omaha, NE 68131. E-mail: [email protected] © 2003, Mosby, Inc. All rights reserved. 0002-8703/2003/$30.00 ⫹ 0 doi:10.1016/S0002-8703(03)00249-7

earlier detection and more accurate characterization of CPF. Although CPF are rare and histologically benign tumors, they may result in life-threatening complications, such as stroke, acute valve dysfunction, embolism, and sudden death.

Data collection A systematic search of the literature using MEDLINE database (National Library of Medicine, Bethesda, Md) was performed to identify all relevant articles using the following key words: cardiac papillary fibroelastoma, papillary fibroelastoma, cardiac valve tumors, primary cardiac tumors, papillary growths of heart, fibroelastoma, giant Lambl excrescences, and valvular excrescences. The references of the articles were examined for additional cases. All foreign language articles were translated with the help of other physicians familiar with those languages. All articles were evaluated by one of the authors. Data were extracted from all case reports and case series, and emphasis was placed to provide a comprehensive overview of the subject. Seven hundred and twenty-five cases of CPF

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Figure 1

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Figure 2

Age at diagnosis of cardiac papillary fibroelastoma (n ⫽ 296 patients).

3–217

were identified. All cases were examined for demographics, clinical characteristics, pathological findings, and treatment of CPF. Statistical analyses were performed using computer software, SPSS 7.0 (SPSS Inc, Chicago, Ill).

Results All 725 cases described in this report had histopathological confirmation of CPF by complete excision or examination at autopsy. Sex data were accurately available in 517 patients. Among these, 286 patients (55%) were male and 231 were female (45%). Ten were children aged ⬍10 years. Age prevalence was accurately available in only 296 patients, and it was highest in the 8th decade of life (Figure 1). The youngest patient reported was a newborn child and the oldest was 92 years of age. No clear risk factor association was noted for the development of this tumor. The size of the tumor varied from 2 mm to 70 mm. Data on the location of tumor were available in 87% of cases (n ⫽ 611 patients). Valvular surface (n ⫽ 511 patients) was the predominant location of tumor, comprising 73% of the total cases and 84% of the cases with data available on the location (Figure 2). In 223 patients (44%), the tumor was located on the aortic valve, followed by mitral valve in 180 patients (35%), tricuspid valve in 65 patients (15%), and pulmonary valve in 43 patients (8%). The left ventricle was the predominant nonvalvular site of tumor origin (55 patients). The other sites involved were the left atrium (n ⫽ 10 patients), left atrial appendage (n ⫽ 2 patients), atrial septum (n ⫽ 8 patients), right atrium (n ⫽ 12 patients), right atrial appendage (n ⫽ 1 patient), Eustachian valve (n ⫽ 2 patients), and right ventricle (n ⫽ 9 patients). Thirty-eight patients had multiple

Location of cardiac papillary fibroelastoma (n ⫽ 611 patients).

tumors on 1 or multiple locations. One patient had 8 tumors at various locations in the heart. The most common clinical presentation was of transient ischemic attack or stroke (n ⫽ 120 patients). The other manifestations were angina (n ⫽ 49 patients), myocardial infarction (n ⫽ 28 patients), sudden death (n ⫽ 21 patients), heart failure (n ⫽ 24 patients), presyncope or syncope (n ⫽ 12 patients), pulmonary embolism (n ⫽ 3 patients), blindness (n ⫽ 7 patients), mesenteric ischemia (n ⫽ 2 patients), peripheral emboli (n ⫽ 3 patients), and renal infarction (n ⫽ 1 patient). In patients with mitral valve tumors, stroke was the most common clinical presentation, but in patients with aortic valve tumors, sudden death and myocardial infarction were the 2 most common presentations. In a large number of patients, tumors were identified as incidental findings at autopsy (n ⫽ 209 patients) or at surgery for other cardiac reasons (n ⫽ 9 patients). The imaging modality predominantly utilized for detection of CPF was transthoracic or transesophageal echocardiography. Other imaging modalities used were cardiac magnetic resonance and computed tomography of the chest. Thrombus was reported on the surface of the tumor in 19 cases but anticoagulation therapy, either with heparin or warfarin sodium, was used in 57 cases. In 3 cases, recurrent stroke occurred while on anticoagulation therapy. Surgical excision was used in 325 patients. In addition to the surgical excision of the tumor, valve repair was required in 39 patients and valve replacement in 42 patients (Figure 3). All specimens removed at autopsy or at surgery were confirmed on histopathological examination. No recurrence of CPF has been reported; the longest postoperative follow-up available was of 11 years. Twenty-five patients who did not have surgery but had adverse outcome data reported were used to determine the independent predictors of adverse out-

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Figure 3

for the first time. In the past few decades, CPF has progressed from a disease diagnosed mainly at autopsy to a disease with a reasonably rapid ante-mortem diagnosis and curative operative therapy.

Epidemiology and natural history

Surgical procedure for papillary fibroelastoma (n ⫽ 425 patients).

come (death or nonfatal embolization). Of these 25 patients, 12 patients had CPF-related death, 11 of which occurred due to obstruction (from mobile tumor on aortic valve) or embolization of the coronary arteries. One death occurred due to right ventricular out flow tract obstruction from a CPF located on the pulmonic valve. Four patients had nonfatal embolization (2 coronary, 1 cerebral, 1 pulmonary). Stepwise logistic regression analysis was used to identify the independent predictors of CPF-related death or nonfatal embolization. Variables included in the analysis were age, sex, tumor location, tumor size, and tumor mobility. By univariate analysis, tumor mobility (P ⫽ .0001) and aortic valve location (P ⫽ .003) were predictors of CPF-related death or nonfatal embolization. The stepwise selection method for variable entry was based on the significance of the score statistic, and removal based on the probability of a likelihood-ratio statistic based on the maximum partial likelihood estimation. The only independent predictor of CPF-related death or nonfatal embolization was tumor mobility (P ⬍ .001).

Discussion Historical perspective Yater,6 in 1931, was the first to describe the valvular tumors, based on 25 previous reports and 2 new cases. In 1934, Campbell and Carling7 gave a description of a patient with sudden death related to the tumor located on the aortic valve. In 1975, Cheitlin et al 29 used the term ‘papillary fibroelastoma’ for the first time, and in the same year, Fishbein et al30 described ultrastructural and electron microscopic characteristics of CPF. Anderson et al,33 in 1977, reported the first and the only case of a neonate with a congenital CPF. Lichtenstein et al35 were the first to report a CPF found incidentally during an operation for ventricular septal defect repair in 1979, and Flotte et al36 diagnosed this tumor on echocardiography in 1980. In 1998, Speights et al158 performed cytogenetic studies

Although CPF occurs in all age groups, ranging from the neonate period to the 10th decade of life, it clearly predominates in adults and is particularly frequent between the 4th and 8th decades of life. Mean age of detection is approximately 60 years. Male sex predominates in most series. Most cases are probably acquired, but the etiology is not known.9,11,33 CPF always occur sporadically. Few cases are congenital, but familial occurrence has not been reported. Long-term longitudinal follow-up studies utilizing echocardiography have not been done, and therefore, the natural history of these tumors has not been defined. On few occasions, development of CPF has been noted to occur over a period ranging from 6 months to 15 years.37,86,92,131,139,183,197 In all of these cases except 1, patients had undergone prior open-heart surgery for different indications. The development of symptoms suggestive of valvular heart disease many years after surgery had prompted echocardiographic investigation, which resulted in identification of CPF. Cardiac papillary fibroelastomas are generally slow growing tumors but may serve as a nidus, allowing formation of large superimposed thrombi over a short period of time.139

Gross pathology Grossly, CPF has a characteristic flower-like appearance with multiple papillary fronds attached to the endocardium by a short pedicle.23 Papillary fronds are narrow, elongated, and branching. They merge imperceptibly into the substance of the valve, and are best visualized when immersed in water or saline. Putting the excised tumor in a physiological saline solution immediately after excision typically results in the seaanemone–like appearance, thus providing easy morphological verification of the tumor being a CPF. A case of cystic CPF has also been described.90 The majority of tumors are around 10 mm in their greatest dimension, but tumors as large as 70 mm have been reported.204 The gross appearance of a characteristic papillary structure may be obscured by attached organizing thrombi.125 CPF usually develop on the cardiac valves, but may arise anywhere in the heart. About 77% of CPF originate on the valves, and the other 23% in the endocardial nonvalvular surface. More than 95% arise in the left heart. The valvular CPF may arise from the free edge of the valve, but more commonly they arise from the mid portion of the valve. The CPF that originate from the semilunar valves may project into ventricular

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or, more frequently, arterial lumen. Those originating on the atrioventricular valves project into the atria. In addition, CPF have been reported to originate from the left ventricle,40,126,132 ostium of the right coronary artery,17,150,159 ostium of the left coronary artery,56,193 left atrial appendage,174,204 atrial septum,95,195 ventricular septum,83,86,133,197 right atrium,24,88 left ventricular outflow tract,78 Eustachian valve and chiari network,76,79,117 right atrial appendage,62 and right ventricular outflow tract.33 CPF are usually solitary, but can rarely be multiple, at the same98,171 or different locations in the heart.37,161 A CPF with attachments to both the mitral valve and left ventricular outflow tract by separate stalks has also been reported.125

did demonstrate active participation of the surface endothelial lining cells with excessive formation of basal membrane material in the formation of CPF. In another immunohistochemical study on CPF, Grandmougin et al200 demonstrated presence of dendritic cells and remnants of cytomegalovirus in the intermediate layers of the tumor and a centrifugal mesenchymal cellular migration from the central layers toward the superficial layer with differentiation steps. The presence of dendritic cells and remnants of cytomegalovirus suggests a possibility of a virus-induced tumor, therefore evoking the concept of a chronic form of viral endocarditis as an underlying mechanism of CPF formation.

Microscopic pathology

Most CPF are found incidentally at the time of echocardiography, cardiac catheterization, cardiac surgery, or autopsy.68 Symptomatic patients with CPF may present with a wide range of symptoms, which are commonly cardiovascular in nature. The clinical presentation is determined by many factors, including tumor location, size, growth rate, and tendency for embolization. The most common clinical presentations are by embolism to the cerebral, systemic or coronary arterial circulations, followed by heart failure and sudden death.42,133,203 Occasionally, CPF have manifested with pyrexia, which abated after successful removal of the tumor.194,211 In 1 case CPF was found to be associated with antiphospholipid antibody syndrome,101 and in another with thyroid dysfunction.173 Recently, a case of CPF has been reported with symptomatic thrombocytopenia, which was relieved by removal of the tumor.214 Cardiac papillary fibroelastomas are firmly attached to valvular or mural endocardium and dislodgement of a CPF, therefore, would appear unlikely. However, embolization may occur from the fragile papillary fronds of the tumor itself or from a thrombus formed on the tumor, although it is not clear whether embolization is more likely to be from associated thrombi or tumor. The histologically confirmed tumor fragments have been isolated from the embolic material from coronary, pulmonary, and peripheral arteries.18,42,70,105 Because most CPF are located in the left heart (⬎95%), systemic embolism in particular is frequent. In a majority of CPF cases with embolism, the cerebral arteries, including retinal arteries, are affected, and transient ischemic attack, stroke, and sudden visual loss have been reported.39,41,52,54,58,65,73,100,105,109,110,142,162,176,209 Occlusion of the coronary arteries leading to angina pectoris and myocardial infarction, and embolization to the peripheral arteries has also been well documented.18,21,42,74,96,102,105,119,128, 133,146,180,189,203,204 Peripheral emboli from CPF have caused mesenteric ischemia, renal infarction, and limb ischemia.21,42,79,169,204 In cases of right heart CPF, clinically evident embolic

Cardiac papillary fibroelastomas are avascular papillomas with a single layer of endocardial cells covering the papillary surface.125 Matrix consists of proteoglycans, elastic fibers, and rarely spindle cells that resemble smooth muscle cells or fibroblasts. The layer of elastic fibers is a hallmark of this tumor but their distribution could be variable; hence, some sections of tumor may fail to demonstrate their presence. Elastica Van Gieson and Movat’s pentachrome stains are especially useful for delineating these components. Two cases of surgically resected CPF with histological evidence of dystrophic calcification have been reported.151 The connective tissue of CPF contains mature collagen with irregular elastic fibers that are longitudinally oriented.29,36 Fibroblasts and more primitive mesenchymal cells are present within the matrix, and the surface endothelial cells are hyperplastic and possess numerous organelles and pinocytic vesicles. The surface cells ultrastructurally resemble endothelial cells, justifying the use of the term endocardial papillary fibroelastoma.29 Although the CPF is a morphologically distinctive cardiac lesion, its histogenesis remains controversial. Rubin et al106 performed an immunohistochemical investigation on 11 cases of CPF, and for comparison, 9 cardiac myxomas and 8 organizing thrombi were also studied. The cells covering the surface of both CPF and cardiac myxoma were positive for vimentin, factor VIII-related antigen, and CD34, in keeping with their presumed vascular endothelial origin. The surface lining cells were also positive for S-100 protein in all CPF and in 8 of 9 cardiac myxomas. In CPF, collagen type IV showed multilayered linear staining beneath the surface that was virtually identical to the staining pattern for elastic tissue. The major immunophenotypic difference between CPF and cardiac myxoma was the frequent presence of muscle-specific actin in the stellate cells of the stroma in cardiac myxoma but not in CPF. Although the study did not clarify whether CPF is a hamartomatous, neoplastic or reparative process, it

Clinical manifestations

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events are rare. Nevertheless, there have been reports of embolization of thrombi or tumor fragments into the pulmonary vessels, with subsequent development of pulmonary hypertension, as well as lethal fulminant pulmonary embolism.24,96,74,106 In the presence of anatomically patent foramen ovale, right-to-left shunting may result in paradoxical embolism from the rightsided CPF.165 Depending on their size and mobility, atrioventricular valve CPF can cause obstruction to filling of left or right ventricle resulting in recurrent pulmonary edema and right-heart failure. These features can mimic the clinical picture of mitral or tricuspid valve stenosis.89 If the tumor is large enough, soft, and easily deformable, and if it has a long stalk, temporary complete obstruction of the orifice of the mitral or tricuspid valve may occur, resulting in syncope or sudden death.79,89,103,112,129,156,168,193,203,204 CPF arising from the aortic valve have been implicated in occurrence of sudden death in otherwise healthy young persons by causing transient or complete obstruction of the ostium of the right or left coronary artery.50,159,164,192 Conduction system disturbances and complete atrioventricular conduction block have also been reported.120 The motion of a CPF back and forth between atrium and ventricle may hamper valve closure and damage the atrioventricular valve apparatus leading to mitral or tricuspid insufficiency, in addition to stenosis. Predominant or isolated valvular insufficiency, although rare, can occur.114,175 Because of narrowing of the left or right ventricular outflow tract, ventricular CPF may present with symptoms of aortic or pulmonic valve stenosis. The systolic murmurs due to interference with closure of the atrioventricular valves or narrowing of the ventricular outflow tracts, and diastolic murmurs due to obstructed filling of the ventricles might be heard in patients with CPF, depending on the size, location, and mobility of the tumor. The intensity of murmur may change on changing body position. The classic diastolic tumor plop, which is heard in one third of patients with atrial myxoma, has not been described with CPF, except in 1 case where a tricuspid valve CPF was associated with a tumor plop.46

Diagnosis Most cases of CPF have been discovered incidentally while the patients were being evaluated for an unrelated problem or physical finding. Electrocardiographic findings are nonspecific, but on occasion, patients may have atrial arrhythmias. Transthoracic echocardiography is a useful tool for the initial evaluation of suspected CPF, whereas transesophageal echocardiography is frequently required for a more comprehensive and accurate assessment. Echocardiography usually demonstrates a small, mobile, pedunculated or sessile

valvular or endocardial mass, which on many occasions flutters or prolapses into the cardiac chambers during systole or diastole. Cardiac papillary fibroelastomas may appear speckled with echolucencies and a stippled pattern near the edges, which correlates with the papillary projections on the surface of the tumor.107,122,132 Chest roentgenograms may reveal an associated enlargement of cardiac chambers, and signs of pulmonary hypertension and congestion, if the tumor is occluding the mitral valve. Very rarely, calcification of CPF makes it visible on routine radiographic examination. The computed tomography is inferior to the echocardiography in depicting the small moving structures, such as on the cardiac valves, because it does not allow true real-time imaging and the imaging planes are limited to those allowed by angulation of the gantry.53,150,210 The magnetic resonance imaging is more valuable than computed tomography because it allows imaging in multiple planes and better soft-tissue characterization of the tumor.212,213 Magnetic resonance imaging typically demonstrates a CPF mass on a valve leaflet or on the endocardial surface of the affected cardiac chamber.154,161,182 Gadolinium may increase the conspicuity of a tumor by showing the differential enhancement with respect to the surrounding normal cardiac structures. Furthermore, valvular CPF can result in turbulence of blood flow, which may be demonstrated with cine gradient-recalled echo magnetic resonance imaging.212 The main disadvantage of MR imaging is its susceptibility to motion artifact. Cardiac catheterization and selective angiography is not usually necessary in most patients with CPF, because adequate information can usually be obtained by noninvasive imaging. Cardiac catheterization appears warranted in cases where the other techniques have not fully defined the CPF or another cardiac condition warranting cardiac catheterization is suspected. In case of intracavity tumors, a filling defect may be observed on angiogram.69,77 On coronary angiography, the total occlusions of the coronary arteries as well aneurysmal dilatations and narrowing of distal coronary branches due to tumor emboli can be disclosed.153,174 In contrast to noninvasive diagnostic techniques, cardiac catheterization can be associated with an added risk to patients because the catheter may dislodge a fragment of the tumor or adherent thrombi, resulting in embolism.

Differential diagnosis Differential diagnosis of CPF primarily encompasses other heart tumors, thrombi, vegetations, valvular calcification, and Lambl’s excrescences. Cardiac myxoma is a predominant left atrial tumor, and is usually attached to the atrial septum by a stalk. Histologically, myxoma differs from CPF by presence of polygonal

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myxoma cells and blood vessels within papillae.125 The papillae of CPF are devoid of blood vessels. Calretinin staining may be a useful way to distinguish between myxoma and CPF.218 Cardiac fibroma, which is a separate entity, frequently demonstrates calcification and cystic degeneration. Cardiac rhabdomyomas are predominant myocardial neoplasms seen in infants and children.214 Metastatic tumors of the heart are more frequent than the primary tumors.1 Unlike CPF, malignant tumors commonly involve the pericardium and myocardium, and are usually accompanied by systemic symptoms. However, with both primary and metastatic tumors, the clinical course may be complicated by emboli. Atrial thrombi are typically located in the atrial appendage, and are associated with atrial fibrillation, atrial dilatation and mitral valve disease. Ventricular thrombi occur in regions of ventricular aneurysm and akinesis, both of which are usually secondary to myocardial infarction or cardiomyopathy. Echocardiographic features of cardiac thrombi differentiating them from CPF include a laminated appearance, irregular or lobulated border, microcavitations, and absence of pedicle. Another lesion that needs to be differentiated from CPF is valvular vegetation. The valvular location and mobility of the infective vegetations could be similar to that of a CPF. However, these vegetations are usually associated with clinical signs of endocarditis and valvular destruction, and may resolve or change in appearance over time with treatment.208 The Libman-Sacks and thrombotic vegetations are located on any part of the leaflet, are generally rounded and sessile, have heterogeneous echoreflectance, and lack independent mobility. Mitral annular calcification, one of the most common echocardiographic findings among elderly patients, should be easily differentiated from a CPF, based on their characteristic location and calcification.219 Lambl’s excrescences, described first by Lambl in 1856,4 are filiform fronds that occur by definition at sites of valve closure, and may be seen without any cardiac disease.15,25 They appear to be wear-and-tear lesions that originate as small thrombi on the endocardium of the contact margins of the valves at the site of minor endothelial damage. They consist of an acellular fibrous axis, which demonstrates a concentric granular pattern related to the organization of successful layers of fibrin with abundance of acid mucopolysaccharide matrix.142 More complex forms resulting from adherence of multiple adjacent excrescences that grow large have been called giant Lambl’s excrescences.15,146 In atrioventricular valves, Lambl’s excrescences are found at the site of valve closure on the atrial surface, but on the semilunar valves they can occur anywhere on the valve. Lambl’s excrescences usually do not occur on the arterial side of the semilunar valves or on the mu-

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ral endocardium, unlike CPF. Lambl’s excrescences have been reported in up to 85% of adults, but CPF is a rare tumor. Lambl’s excrescences are multiple in ⬎90% of cases, but CPF are rarely multiple. The CPF can be distinguished from Lambl’s excrescences by their composition, size, and location.34,81,179,142,211 They are larger and more gelatinous than Lambl’s excrescences, and are present on valves, away from the valvular lines of closure, and also on the endocardial surfaces of the atria or ventricles. A shared pathogenesis of CPF and Lambl’s excrescences has been suggested.81,141 It has been proposed that endocardial tissue may, in response to shear stresses or possible congenital factors, proliferate in a unique way, resulting in avascular fronds that, in places away from normal areas of stress, are classified as CPF, and smaller more common lesions near lines of closure are considered Lambl’s excrescences.

Treatment Surgical excision of CPF is curative, and in most cases, the tumors can be easily removed because they are pedunculated.99,107,163,168 Therefore, the treatment of choice for symptomatic CPF is surgical excision. The root of the pedicle and the full thickness of endocardium involved is excised, and any resulting defects is closed by direct suturing or, if too large, with a pericardial or Dacron patch. Care is taken to avoid intraoperative fragmentation of the tumor and embolism. All chambers of the heart are inspected to rule out multiple tumors. Mechanical damage to a heart valve or adhesion of the tumor to valve leaflets may call for valve repair or replacement.147 The symptomatic patients who are not surgical candidates could be treated with long-term oral anticoagulation, although no randomized controlled data are available on its efficacy.113,186 Asymptomatic patients could be treated surgically if the tumor is mobile, as the tumor mobility is the independent predictor of death or nonfatal embolization. Asymptomatic patients with nonmobile CPF could be followed-up closely until symptoms develop or tumor becomes mobile; however, none of these recommendations are based on the randomized controlled data because no such data have been reported. Video-assisted surgery greatly facilitates exposure and excision of the CPF masses.132 Various methods have been proposed for complete excision of left-sided CPF to avoid a left ventriculotomy with its subsequent complications. When a CPF is located on the aortic valve or the left ventricular outflow tract, it is best approached via the transaortic route, and when located on the mitral valve, it is best approached via a left atriotomy.131,132,184 For the tumors deep within the left ventricular cavity close to the apex, the use of a cardioscope passing through the aortic or mitral valve is recommended to avoid damage to the valvular appara-

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tus and to achieve complete surgical excision.184 Intraoperative transesophageal echocardiography is done to assess valvular function after excision of the valvular CPF.

Prognosis Surgery is curative and the short- and long-term prognosis after surgical removal is excellent. Recurrence after surgical resection has not been reported; the longest follow-up reported is of 11 years. Most patients underwent transthoracic echocardiography for follow-up evaluations. Tumor mobility is an independent predictor of occurrence of death or nonfatal embolization.

Conclusions Although CPF is a histologically benign tumor, the clinical course could be devastating because of its strategic position, which includes systemic or pulmonary embolism and death. Echocardiography, particularly transesophageal echocardiography, complemented by cardiac magnetic resonance imaging, provides the degree of structural resolution necessary to ascertain the location and the extent of anatomic and hemodynamic involvement. The ultimate diagnosis is based on the

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characteristic histopathological features. Surgery should be offered to all symptomatic patients because the successful complete resection of a CPF is curative and the long-term postoperative prognosis is excellent. The symptomatic patients who are not surgical candidates could be offered long-term oral anticoagulation, although no randomized controlled data are available on its efficacy. Surgery could also be offered to asymptomatic patients if the tumor is mobile, because the tumor mobility is the independent predictor of death or nonfatal embolization. Asymptomatic patients with nonmobile CPF could be followed-up closely with periodic clinical evaluation and echocardiography, and intervene surgically when symptoms develop or tumor becomes mobile. These recommendations made for the management of CPF are not based on randomized controlled studies because no such studies have been reported, and hence the recommendations are likely to be amended as such data become available. We thank Rachid Daoui, MD, Darmadi Khong, MD, Braulio Cosme-Thornmann, MD, Ketan Jani, MD, and Nilesh Patel, MD for translating the foreign language articles.

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